CORRELATION OF NEUTROPHIL-LYMPHOCYTE RATIO (NLR) AND PLATELET-LYMPHOCYTE RATIO (PLR) WITH COMPLICATIONS AND POSTOPERATIVE SURVIVAL IN SURGERY FOR BONE METASTASIS OF THE APPENDICULAR SKELETON / CORRELAÇÃO DO NEUTROPHIL-LYMPHOCYTE RATIO (NLR) E PLATELET-LYMPHOCYTE RATIO (PLR) COM COMPLICAÇÕES E SOBREVIDA PÓS-OPERATÓRIAS NA CIRURGIA PARA METÁSTASE ÓSSEA DO ESQUELETO APENDICULAR

Introduction: Bone metastasis is the most common malignant neoplasm of the skeleton, and surgical decision-making depends on multiple factors, including postoperative complications and life expectancy. The identification of new prognostic factors can assist in decision making. Objective: In long bones metastases, to analyze the incidence of complications and postoperative survival up to 1 year, correlating them with NLR and PLR. Method: Review of 160 medical records of patients who underwent surgery for bone metastasis in the appendicular skeleton. In addition to epidemiological characteristics, NLR and PLR values were determined, correlating them with survival and complications. Result: Women represented 64.5% with a primary breast tumor in 62.6%; the proximal femur was the most affected; median survival was 13.2 months and in 1 year 34.7%. Tumor resection with endoprosthesis was more common. The post-surgical complication rate was 10% and the average time for post-operative complications to occur was 27.9 days (0-140). An association between the neutrophil variable and postoperative complications was found (p=0.04). For every 100 more units of neutrophils there was a 1% increase in the chances of post-surgical complications. Mean NLR and PLR values were, respectively, 5.3 (0.2-30.7) and 199.7 (32.1-676.7). Patients with NLR NLR ≥ 2 (p<0,001) showed a decrease in survival from 92,3% to 62,5% at the 3rd month, and from 61,5% to 31,3% at 1 year. Those with PLR ≥209 (p<0.001) showed a decrease in survival from 69% to 59.3% at the 3rd month, and from 40.2% to 25.9% at 1 year. Conclusion: There was no positive association between NLR and PLR with postoperative complications, but strongly yes with survival from the 3rd month after surgery.

Introdução: Metástase óssea é a neoplasia maligna mais comum do esqueleto, e a tomada de decisão cirúrgica depende de múltiplos fatores, incluindo as complicações pós-operatórias e a expectativa de vida. A identificação de novos fatores prognósticos pode auxiliar na tomada de decisão. Objetivo: Analisar em metástases de ossos longos, a incidência de complicações e sobrevida pós-operatórias até 1 ano correlacionando-as com NLR e PLR. Método: Revisão de 160 prontuários de operados por metástase óssea no esqueleto apendicular. Além de características epidemiológicas, foram determinados os valores de NLR e PLR correlacionando-os com sobrevida e complicações. Resultado: Mulheres representaram 64,5% com tumor primário na mama em 62,6%; o fêmur proximal foi o mais acometido; sobrevida média foi 13,2 meses e a de 1 ano 34,7%; ressecção tumoral com endoprótese foi mais comum. A taxa de complicação pós-cirúrgicas foi de 10% e o tempo médio para a ocorrência de complicações pós-operatórias foi de 27,9 dias (0-140). Foi encontrada associação da variável neutrófilos com a complicação pós-operatória (p=0,04). A cada 100 unidades a mais de neutrófilos houve aumento de 1% nas chances de complicações pós-cirúrgicas. Valores médios do NLR e PLR foram, respectivamente, 5,3 (0,2-30,7) e 199,7 (32,1-676,7).  Os pacientes com NLR ≥ 2 (p<0,001) apresentaram diminuição na sobrevida de 92,3% para 62,5% no 3° mês e de 61,5% para 31,3% em 1 ano. Aqueles com PLR ≥209 (p<0,001) apresentaram diminuição na sobrevida de 69% para 59,3% no 3° mês, e de 40,2% para 25,9% em 1 ano. Conclusão: Não foi verificada associação positiva entre o NLR e o PLR com complicações pós-operatórias, mas com sobrevida fortemente sim, a partir do 3° mês de pós-operatório.

CAN NEUTROPHIL-LYMPHOCYTE RATIO (NLR) AND PLATELET-LYMPHOCYTE RATIO (PLR) BE PROGNOSTIC INDICATORS FOR OPERATIVE COMPLICATIONS AND SURVIVAL IN BONE METASTASES? / NEUTROPHIL-LYMPHOCYTE RATIO (NLR) E PLATELET-LYMPHOCYTE RATIO (PLR) PODEM SER INDICADORES DE PROGNÓSTICO PARA COMPLICAÇÕES OPERATÓRIAS E SOBREVIDA EM METÁSTASES ÓSSEAS?

Introduction: In general, inflammation stimulates the production and release of neutrophils and, at the same time, decreases the production of lymphocytes. Lymphopenia reflects that cell-mediated immunity is impaired, while neutrophilia represents a response to systemic inflammation in these cancers. Objective: To review the incidence of complications and postoperative survival rates in patients with bone metastases in long bones, correlating them with markers NLR and PLR. Method: Narrative review carried out collecting information published on virtual platforms in Portuguese and English, initially carried out by searching for descriptors related to the topic, which were: "lower extremity, surgery, metastasis, epidemiology, postoperative complications, neutrophils, lymphocytes, platelets". The extension incorporated AND or OR, by title and/or summary, and full reading of the texts most related to the topic. Result: 21 articles were included. Conclusion: The higher both the NLR and PLR are associated with lower survival in patients with bone metastases when undergoing surgical treatment, especially after 3 months postoperatively. However, there is still no confirmation that they signal any outcome, favorable or not, in relation to postoperative complications.

Introdução : De um modo geral, a inflamação estimula a produção e liberação de neutrófilos e, ao mesmo tempo, diminui a produção de linfócitos. A linfopenia reflete que a imunidade mediada pelas células é prejudicada, enquanto a neutrofilia representa resposta à inflamação sistêmica nesses cânceres. Objetivo : Revisar nos pacientes com metástase óssea em ossos ao longo da incidência de complicações e taxas de sobrevida pós-operatória correlacionando-as com os marcadores NLR e PLR. Método : Revisão narrativa feita colhendo informações publicadas em plataformas virtuais em português e inglês inicialmente realizada por busca dos descritores relacionados ao tema que foram: "extremidade inferior, cirurgia, metástase, epidemiologia, complicações pós-operatórias, neutrófilos, linfócitos, plaquetas" e seus equivalentes em inglês " extremidade inferior, cirurgia, metástase, epidemiologia, sobrevivência, complicações, neutrófilos, linfócitos, plaquetas sanguíneas ". A extensão incorporou AND ou OR, pelo título e/ou resumo, e leitura na íntegra dos textos mais relacionados ao tema.  Resultado : Foram incluídos 21 artigos. Conclusão : Quanto maiores, tanto o NLR quanto o PLR estão associados à menor sobrevida em pacientes com MO quando submetidos ao tratamento cirúrgico, especialmente após 3 meses de pós-operatório. Contudo, ainda não há confirmação de que eles sinalizam algum estágio, positivo ou não, em relação às complicações pós-operatórias.

Efficacy and safety of EGFR-TKI combined with WBRT vs. WBRT alone in the treatment of brain metastases from NSCLC: a systematic review and meta-analysis.

Background: The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined. Methods: A systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023. Results: This analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42-1.74, p < 0.001), increases the intracranial disease control rate (RR = 1.30, 95% CI: 1.23-1.37, p < 0.001), and enhances the 1-year survival rate (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001). Additionally, this combined treatment was associated with a significant survival advantage (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001) and a reduced incidence of adverse effects (RR = 0.65, 95% CI: 0.51-0.83, p < 0.001), particularly with respect to nausea and vomiting (RR = 0.54, 95% CI: 0.37-0.81, p = 0.002) and myelosuppression (RR = 0.59, 95% CI: 0.40-0.87, p = 0.008). However, no statistically significant differences were observed for diarrhea (RR = 1.15, 95% CI: 0.82-1.62, p = 0.418), and skin rash (RR = 1.35, 95% CI: 0.88-2.07, p = 0.164). Conclusion: In contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566.

Case report: [18F]FAPI-42 PET/CT visualize primary adenoid cystic carcinoma not detected by [18F]FDG.

Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer. Still, its growth and invasion progress is slow, and its hematogenous metastasis is ACC's most common distant metastasis. Because of the broad expression and low background uptake of fibroblast activation protein (FAP) in tumor stroma, FAPI is considered another potential tracer of ACC in addition to FDG. In this case, we report a patient who was diagnosed with metastatic ACC liver cancer by fine needle aspiration biopsy (FNAB) and underwent PET/CT examination of [18F]FDG and [18F]FAPI-42 to find the primary cancer lesion. Finally, the primary cancer lesion was found in the left submandibular gland and was pathologically confirmed as ACC after resection.

Ptosis secondary to orbital metastasis undetected by magnetic resonance imaging: A case report.

We report a patient with isolated ptosis secondary to orbital metastasis but no evidence of a neoplastic process on magnetic resonance imaging (MRI). A 69-year-old male was referred to our hospital with ptosis of the right upper eyelid and secondary frontalis muscle overaction on the left side for six months. The palpebral fissure was 3mm on the right and 16mm on the left, and levator function was 6mm and 19mm respectively. Three years previously, he had undergone surgical resection of the left lower lobe of the lung due to a T1 N0 M0 adenocarcinoma, and no recurrence had since been observed. An MRI was performed to rule out ptosis secondary to metastasis. Thyroid dysfunction and myasthenia were also ruled out. The ptosis was attributed to an isolated microvascular third nerve palsy. A standard external levator advancement was performed. Six months after the surgery, the patient presented with intense pain, minimal ptosis, edema and diplopia. A new MRI revealed an orbital metastasis measuring 2.4×1.0×1.6cm in the superior orbit, exerting mass effect on the superior rectus and the levator palpebrae superioris muscle. A positron emission tomography scan revealed a recurrence of the lung cancer with multiple bony metastases. The patient underwent chemotherapy consisting of the taxol-carboplatin protocol. Our report highlights the importance of a high index of suspicion of a neoplastic etiology in patients with mild symptoms and a history of cancer even if imaging does not initially reveal a mass or infiltration.

Radiation therapy of the primary tumour and/or metastases of digestive metastatic cancers.

Metastatic gastrointestinal cancer is not an uncommon situation, especially for pancreatic, gastric, and colorectal cancers. In this setting, few data are available on the impact of the treatment of the primary tumour. Oligometastatic disease is associated with longer survival in comparison with more advanced disease. Metastasis-directed therapy, such as stereotactic body radiotherapy, seems related to better outcomes, but the level of evidence is low. In most tumour locations, prospective data are very scarce and inclusion in ongoing trials is strongly recommended.

Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Excessive MALAT1 promotes the immunologic process of neuromyelitis optica spectrum disorder by upregulating BAFF expression.

Increased B cell activating factor (BAFF) expression in patients with neuromyelitis optica spectrum disorder (NMOSD) is associated with B cell overstimulation, but the underlying mechanism remains unclear. This study aimed to reveal the emerging mechanisms that regulate BAFF expression in the inflammatory process of NMOSD. The results showed that the expression of miR-30b-5p was significantly decreased in NMOSD CD14+ monocytes compared with the normal control. Furthermore, we confirmed that metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) is an upstream target of miR-30b-5p, and it could act as a ceRNA and absorb miR-30b-5p with reduced expression of miR-30b-5p. The low expression of miR-30b-5p could not bind to BAFF messenger RNA (mRNA), which resulted in the overexpression of both BAFF mRNA and protein expression. Overexpression of BAFF could bind to the corresponding receptors on B cells, which may initiate activation and proliferation of B cells and increase their production of autoantibodies. Therefore, these findings interpreted that excessive MALAT1 expression in NMOSD mononuclear macrophages led to increased BAFF expression by targeting miR-30b-5p, which caused B cell autoimmune reaction and autoantibodies production, aggravated the disease progression of NMOSD.

[Ocular and non-ocular squamous cell carcinomas in the Haflinger: Eight cases at the Institut Suisse de Médecine Equine (2015-2022)]. / Okuläre und nicht-okuläre Platten­-epithel­karzinome beim Haflinger: Acht Fälle am Institut Suisse de Médecine Equine (2015­2022).

INTRODUCTION: This case series describes the clinical course of ocular and non-ocular squamous cell carinoma (SCC) in the Haflinger horse and is intended to raise awareness of the high recurrence rate and tendency to metastasize. Eight Haflingers with histologically confirmed SCC were included, five ocular and three non-ocular, who were presented at the Institut Suisse de Médecine Équine (ISME) Bern between July 2015 and January 2022. The ocular SCC cases were all presented because of an apparent mass, which in most cases was post-treatment recurrence. The occurrence of recurrences was observed between 3 weeks and 16 years after initial therapy. Four of five Haflingers with ocular SCC had an enucleation, three of which were clinically normal at the time of the completion of this study, one case was euthanized due to confirmed metastases and one due to lameness. The result of enucleations for therapy of ocular SCC was good if no metastases occurred. Of the three non-ocular SCC cases, only one case, a penile SCC, had an apparent mass. Therapy was initiated in this case, while the other two cases were euthanized shortly after diagnosis due to the poor prognosis of SCC in the appropriate locations (maxillary sinus, mandible). Metastases occurred three and two years after removal of the primary tumor in ocular SCC in the scapula, liver and lungs and in non-ocular SCC from the penis to the nostrils. Since a postmortem pathological examination was not carried out on all Haflingers, further metastases cannot be ruled out. Haflingers with SCC should be monitored by a veterinarian over the long term, as recurrences and/or metastases can still occur years later.

INTRODUCTION: Cette série de cas décrit l'évolution clinique des carcinomes épidermoïdes (CE) oculaires et non oculaires chez le cheval Haflinger et vise à faire prendre conscience du taux de récidive élevé et de la tendance à la formation de métastases. Huit Haflinger avec un CE confirmé histologiquement, cinq oculaires et trois non-oculaires, qui ont été présentés à l'Institut Suisse de Médecine Équine (ISME) Berne entre juillet 2015 et janvier 2022, ont été inclus. Les cas de CE oculaires ont tous été présentés en raison d'une masse apparente, qui dans la plupart des cas était une récidive post-traitement. La survenue des récidives a été observée entre 3 semaines et 16 ans après le traitement initial. Quatre des cinq Haflinger atteints de CE oculaire ont subi une énucléation, dont trois étaient cliniquement normaux au moment de l'achèvement de l'étude, un cas ayant été euthanasié en raison de métastases confirmées et un autre en raison d'une boiterie. Le résultat des énucléations pour la thérapie du CE oculaire était bon s'il n'y avait pas de métastases. Sur les trois cas de CE non oculaires, seul un cas, un CE pénien, présentait une masse apparente. Le traitement a été initié dans ce cas, tandis que les deux autres cas ont été euthanasiés peu de temps après le diagnostic en raison du mauvais pronostic des CE dans les localisations constatées (sinus maxillaire, mandibule). Des métastases sont apparues trois et deux ans après l'ablation de la tumeur primaire dans le cas du CE oculaire, au niveau de l'omoplate, du foie et des poumons et, dans un cas de CE non oculaire, celui du pénis, aux narines. Étant donné que tous les Haflinger n'ont pas fait l'objet d'un examen pathologique post-mortem, on ne peut exclure la possibilité d'autres métastases. Les Haflinger atteints de CE doivent être suivis à long terme par un vétérinaire, car des récidives et/ou des métastases peuvent encore survenir des années plus tard.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study / Estudo retrospectivo de vida-real, em centro único, para avaliação do comportamento da fosfatase alcalina total após terapia com rádio-223 no câncer de próstata resistente a castração

Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

Metastatic and aggressive renal cell carcinoma mimicking a unilateral choroidal tuberculoma / Carcinoma de células renais metastático grave mimetizando tuberculoma de coroide unilateral

ABSTRACT Ocular metastases from systemic tumors are uncommon. The choroid is the most frequent target, with a preference for elderly individuals. Lung cancer is the predominant primary tumor that metastasizes to the eyes in males, although other ocular conditions such as uveitis and retinal lesions can mimic secondary tumor implants in ocular tissues. On fundoscopy, choroidal metastasis resembles other infectious processes, especially choroidal tuberculoma. Therefore, patients presenting with choroidal masses should undergo detailed clinical examinations, especially if the mass is the first manifestation of a systemic and severe disease. In this report, we describe a young man with a metastatic choroidal tumor secondary to papillary renal cell carcinoma mimicking a unilateral choroidal tuberculoma.

RESUMO A disseminação metastática ocular de tumores sistêmicos é incomum, ocorrendo principalmente na coroide e em pacientes idosos. O câncer de pulmão é considerado o principal tumor metastático ocular em homens, contudo, outras doenças oculares, como as uveítes e lesões retinianas, podem mimetizar os implantes secundários tumorais nos tecidos oculares. O aspecto fundoscópico das neoplasias da coroide pode apresentar similaridade com outros processos infecciosos, especialmente o tuberculoma de coroide. Dessa forma, a investigação clínica detalhada é de grande importância no diagnóstico de pacientes com massas coroideanas, especialmente quando configuram a primeira manifestação de uma doença sistêmica e grave. Relatamos um caso raro de metástase coroideana como primeira manifestação clínica do carcinoma de células renais em um homem jovem, mimetizando um tuberculoma de coroide.

Real-world efficacy and safety of pyrotinib in patients with HER2-positive metastatic breast cancer: A prospective real-world study.

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC). Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records. Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies. Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.

Une lésion labiale inhabituelle.

A 75 years old patient presented with a papular easily bleeding lesion of the lower lip that had been growing for two months. He was known for alcoholic cirrhosis complicated with hepatocellular carcinoma treated since one year. A working diagnostic hypothesis of benign vascular lesion was proposed. Microscopic examination showed a neoplastic dermal proliferation that had been fully excised, made of lobules segregated by thin fibrous septae. The neoplastic architecture was trabecular and delineating spaces forming pseudo-rosettes. Tumour cells were monomorphic, cuboidal or cylindric with abundant eosinophilic and granulous cytoplasm and centered by a lone nucleus that often contained a prominent nucleolus. Some spaces were filled with a brownish-greenish pigmented material. Immunohistochemical study showed that tumour cells were positive with the hepatocyte paraffin 1 antibody as well as cytokeratin 8 antibody. Chromogranin A and synaptophysin stainings were negative. Thus we concluded to a lip metastasis from the previously known hepatocellular carcinoma. Skin metastasis arise in around 3% of cases of hepatocellular carcinoma. They account for less than 1% of all cutaneous metastasis. Overall appearance of cutaneous metastasis of hepatocellular carcinoma is associated with a poor prognosis and an aggravated risk of metastasis to other locations and organs and a median overall survival of less than 5 months. Since incidence of hepatocellular carcinoma is rising pathologists might face more frequently in years to come to cutaneous metastasis whose varied clinical presentations make a diagnostic challenge.

[Duodenal bleeding due to metastasis from lung adenocarcinoma controlled by radiotherapy: A case report and literature review]. / Saignement duodénal dû à une métastase d'un cancer pulmonaire contrôlé par radiothérapie : cas clinique et revue de la littérature.

INTRODUCTION: Gastrointestinal (GI) metastases in lung cancer rarely occur. CASE REPORT: We report here the case of a 43-year-old male active smoker who was admitted to our hospital for cough, abdominal pain and melena. Initial investigations revealed poorly differentiated adenocarcinoma of the superior-right lobe of the lung: positive for thyroid transcription factor-1 and negative for protein p40 and for antigen CD56, with peritoneal, adrenal and cerebral metastasis, as well as anemia requiring major transfusion support. Over 50% of cells were positive for PDL-1, and ALK gene rearrangement was detected. GI endoscopy showed a large ulcerated nodular lesion of the genu superius with active intermittent bleeding, as well as an undifferentiated carcinoma with positivity for CK AE1/AE3 and TTF-1, and negativity for CD117, corresponding to metastatic invasion originating from lung carcinoma. Palliative immunotherapy with pembrolizumab was proposed, followed by targeted therapy with brigatinib. Gastrointestinal bleeding was controlled with a single 8Gy dose of haemostatic radiotherapy. CONCLUSION: GI metastases are rare in lung cancer and present nonspecific symptoms and signs but no characteristic endoscopic features. GI bleeding is a common revelatory complication. Pathological and immunohistological findings are critical to diagnosis. Local treatment is usually guided by the occurrence of complications. In addition to surgery and systemic therapies, palliative radiotherapy may contribute to bleeding control. However, it must be used cautiously, given a present-day lack of evidence and the pronounced radiosensitivity of certain gastrointestinal tract segments.

[Differential diagnostic between hepatocellular carcinoma and hepatoid carcinoma with bone metastasis revelation: What tools can be used?] / Diagnostic différentiel entre un carcinome hépatocellulaire et un carcinome hépatoïde à révélation métastatique osseuse : quels outils sont à disposition ?

Bone metastases of hepatocellular carcinoma (HCC) are rare and disease-revealing bone metastasis are exceptional. Here, we report the case of a 69-year-old man with a cervical vertebral metastasis of hepatocellular carcinoma. Morphological aspect of a metastatic tumor with eosinophilic and polygonal cells raises the question of the differential diagnosis between a localization of a hepatocellular carcinoma or an hepatoid carcinoma, notably when the metastasis is the first clinical manifestation. The morphological aspect by itself does not provide strong enough arguments for diagnosis. Well selected immunohistochemical markers can sometimes help to orientate towards one of the two hypotheses, in particular SALL4 and LIN28 which are in favour of hepatoid carcinoma when both are positive. Finally, as these two entities have different molecular profiles, molecular study can also be helpful to distinguish them. Indeed, HCCs often present TERT promoter, CTNNB1 mutations and IL-6/JAK/STAT pathway activation while hepatoid adenocarcinoma frequently presents chromosome 20 long arm gain. TP53 mutations are found in both entities and are therefore not discriminating. Differential diagnosis is important because the treatment will be that of the primary. Prognostic data for HCC revealed by bone metastasis are scarce, although they seem to be associated with a poor prognosis, with a 1 to 2 months overall survival. There is currently no data for hepatoid adenocarcinoma with bone metastasis.

[Secondary tumors localized in testis]. / Localisations tumorales secondaires testiculaires.

Testis tumors are uncommon in oncology, and testicular metastasis from distant solid tumors are even rarer. We present two cases encountered in our department of pathology in CHU de Rennes, France. Moreover, we collected all reported cases in the Medline/PubMed databases of non-hematopoietic secondary testis tumors in adults, excluding autopsy studies, to propose an integrative study on this topic. In total, we report 98 cases of secondary testis lesions to prostate (n=38, 38.77 %), colorectal (n=19, 19.39%), gastric (n=12, 12.24%), kidney (n=7, 7.14%), lung (n=6, 6.12%) and other primary cancers. The median age at diagnosis was 66.5 years. We identified significantly more prostate adenocarcinoma (P<0.0001) when the primary tumor was known and significantly more colorectal adenocarcinoma (P=0.035) and pancreatic adenocarcinoma (P=0.002) when the primary tumor was unknown. The age at diagnosis was older when the primary tumor was known (P=0.007). We present the challenges for the diagnosis and propose some elements for diagnosis orientation. Finally, we discuss the possible ways of metastatic dissemination from primary site to testis, as illustrated by the two cases we present.

Sociodemographic, clinical and survival profile of adult metastatic patients / Perfil sociodemográfico, clínico y de supervivencia de pacientes adultos metastáticos / Perfil sociodemográfico, clínico e de sobrevida de pacientes adultos metastáticos

ABSTRACT Objective: To characterize the sociodemographic, clinical and survival profile of adult metastatic patients. Method: Retrospective cross-sectional study, with secondary data from an oncology care unit, analyzed using logistic regression, Chi-Square test and Fisher's exact test, Kaplan-Meier and Log-Rank tests. Results: From the 678 patients, male gender, mean age 59.54 years old and low education level prevailed. The mean time between diagnosis and initiation of treatment was 89.50 days (± 58.87). Increased risk of primary cancer in the digestive tract (OR 1.42). Prevalence of adenocarcinoma (OR 1.53) and metastasis to bone (OR 2.59), lymph nodes (OR 1.75), liver and peritoneum (OR 1.42). The mean overall survival was 4.16 months and a median of 3.0 months. Conclusion: The main primary site was the digestive system, and the identification of metastases was predominantly unifocal liver in both genders. Overall patient survival was reduced by cancer progression.

RESUMEN Objetivo: Caracterizar el perfil sociodemográfico, clínico y de supervivencia de pacientes adultos metastáticos. Método: Estudio transversal retrospectivo, con datos secundarios de una unidad de atención oncológica, analizados por: regresión logística, prueba de Chi-Cuadrado y prueba exacta de Fisher, Kaplan-Meier y Log-Rank. Resultados: De los 678 pacientes predominó el sexo masculino, edad media 59,54 años y baja escolaridad. El promedio entre el diagnóstico y el inicio del tratamiento fue de 89,50 días (± 58,87). Mayor riesgo de cáncer primario en el tracto digestivo (OR 1,42). Prevalencia de adenocarcinoma (OR 1,53) y metástasis en hueso (OR 2,59), ganglios linfáticos (OR 1,75), hígado y peritoneo (OR 1,42). La supervivencia global media fue de 4,16 meses y una mediana de 3,0 meses. Conclusión: El principal sitio primario fue el tracto digestivo y la identificación de metástasis fue predominantemente hepática unifocal en ambos sexos. La supervivencia general del paciente se redujo por la progresión del cáncer.

RESUMO Objetivo: Caracterizar o perfil sociodemográfico, clínico e de sobrevida de pacientes adultos metastáticos. Método: Estudo transversal retrospectivo, com dados secundários de uma unidade de assistência oncológica, analisados por: regressão logística, teste de Qui-Quadrado e testes exato de Fisher, Kaplan-Meier e Log-Rank. Resultados: Dos 678 pacientes, prevaleceu o sexo masculino, a idade média 59,54 anos e a baixa escolaridade. A média entre o diagnóstico e o início de tratamento foi 89,50 dias (± 58,87). Maior risco de câncer primário no aparelho digestivo (OR 1,42). Prevalência do adenocarcinoma (OR 1,53) e metástase para o osso (OR 2,59), linfonodos (OR 1,75), fígado e peritônio (OR 1,42). A média de sobrevida global foi de 4,16meses e mediana de 3,0 meses. Conclusão: O principal sítio primário foi o aparelho digestivo e a identificação das metástases foi prevalentemente hepática unifocal em ambos os sexos. A sobrevida global dos pacientes foi reduzida pelo avanço do câncer.

Aplicação da ultrassonografia no diagnóstico e tratamento do câncer de língua / Application of ultrasound in the diagnosis and treatment of tongue cancer

O câncer oral é um problema de saúde pública global e a taxa de sobrevivência para pacientes com câncer de língua tem permanecido relativamente inalterada e insatisfatória, alcançando somente cerca de 50% após cinco anos de acompanhamento. A cirurgia associada ou não à radioterapia permanece como a abordagem terapêutica predominante, com o estadiamento clínico sendo um parâmetro essencial para a estratificação de risco de óbito para os pacientes acometidos. No entanto, a avaliação precisa de características clínicas e microscópicas com potencial de determinação prognóstica é desafiadora, e as técnicas de imagem, como a ultrassonografia, tem sido propostas como importantes auxiliares, apesar de sua eficácia na análise de diferentes características da neoplasia permanecer um campo de amplo debate na literatura. Assim, esta revisão de escopo teve como objetivo avaliar a eficiência e aplicabilidade da ultrassonografia no manejo clínico do câncer de língua. Utilizou-se uma estratégia de busca aplicada a diferentes bases de dados eletrônicas, como Scopus, Web of Science e Pubmed/MEDLINE, além do Google Scholar como base de literatura cinzenta. Os critérios de inclusão e exclusão foram construídos e aplicados para selecionar os estudos mais relevantes para o objetivo do estudo. Ao término do processo de seleção de artigos, um total de 47 estudos foi incluído na presente revisão e investigou-se o uso da ultrassonografia em diferentes momentos clínicos de manejo do câncer de língua, incluindo pré-, trans- e pós-operatório. Os resultados demonstraram que a ultrassonografia foi utilizada e se mostrou confiável para avaliar a espessura e a extensão de profundidade microscópica do tumor, para a identificação de metástases linfonodais, para determinar o status das margens cirúrgicas tumorais e para monitorar o tratamento no contexto pós-operatório. Além disso, a técnica Doppler de ultrassom proporcionou informações valiosas sobre o fluxo sanguíneo na artéria lingual profunda, auxiliando na identificação de áreas com maior neovascularização. Portanto, este estudo ressaltou a importância da ultrassonografia no manejo clínico do câncer de língua, fornecendo dados confiáveis sobre importantes parametros prognósticos, sendo uma ferramenta útil que pode melhorar o índice de sobrevida dos pacientes.

Oral cancer is a global public health problem and the survival rate for patients with tongue cancer has remained relatively unchanged and unsatisfactory, reaching only about 50% after five years of follow-up. Surgery with or without radiotherapy remains the predominant therapeutic approach, with clinical staging being an essential parameter for stratifying the risk of death for affected patients. However, the accurate assessment of clinical and microscopic features with potential for prognostic determination is challenging, and imaging techniques, such as ultrasonography, have been proposed as important aids, although their effectiveness in the analysis of different characteristics of the neoplasm remains a field of wide debate in the literature. Thus, this scope review aimed to evaluate the efficiency and applicability of ultrasound in the clinical management of tongue cancer. A search strategy was applied to different electronic databases, such as Scopus, Web of Science and Pubmed/MEDLINE, in addition to Google Scholar as a gray literature base. Inclusion and exclusion criteria were constructed and applied to select the most relevant studies for the purpose of the study. At the end of the article selection process, a total of 47 studies were included in this review and investigated the use of ultrasound in different clinical moments of tongue cancer management, including pre-, trans- and postoperative. The results demonstrated that ultrasonography was used and proved to be reliable for assessing the thickness and microscopic depth of the tumor, for identifying lymph node metastases, for determining the status of tumor surgical margins, and for monitoring treatment in the postoperative context. In addition, the Doppler ultrasound technique provided valuable information about blood flow in the deep lingual artery, helping to identify areas with increased neovascularization. Therefore, this study highlighted the importance of ultrasound in the clinical management of tongue cancer, providing reliable data on important prognostic parameters, being a useful tool that can improve the survival rate of patients.